118th Meeting Minutes

September 2-3, 2014

The National Advisory Council on Drug Abuse convened its 118th meeting at 2:00 p.m. on September 2, 2014 in Conference Rooms C & D, 6001 Executive Boulevard, Bethesda, Maryland. The closed portion of the meeting on September 2, 2014, was for the purpose of reviewing applications for Federal grant assistance and was open only to Council members and Federal employees. The open portion, which was open to the public on September 3, 2014, began at 8:30 a.m. The Council adjourned on September 3, 2014 at 12:00 p.m.

Council Members Present
Anne Andorn, M.D.
Laura Bierut, M.D.
Regina Carelli, Ph.D.
Nabila El-Bassel, Ph.D., D.S.W.
Carl Hart, Ph.D.
James Hildreth, Ph.D., M.D.
Elizabeth Howell, M.D.
Thomas Kirk, Ph.D.  
Robert Lenox, M.D. 
Kelvin Lim, M.D.
Barbara Mason, Ph.D.
Michael Nader, Ph.D.
Marina Picciotto, Ph.D.
John Rotrosen, M.D.

Council Chair
Nora Volkow, M.D.

Executive Secretary
Mark Swieter, Ph.D., Acting

Federal Employees Present

Members of the Public Present

Emily Smith, M.P.H. - RTI International

Geoffrey Mumford, Ph.D. - American Psychological Association

Closed Portion of the Meeting – September 2, 2014

1. Call to Order

   This portion of the meeting was closed to the public in accordance with sections 552b(c) (4) and 552b(c) (6), Title 5, U.S. Code and section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix 2).
   
   Dr. Nora Volkow, Director, NIDA, called the meeting to order and welcomed the Council and staff.  She reminded those present that the Federal Advisory Committee Act applies to Council meetings and that this portion of the meeting was closed to the public. 
   
   Dr. Mark Swieter, Acting Executive Secretary, summarized relevant NIH policies, provided detailed instructions on Council review procedures, and reminded those present about NIH confidentiality and conflict of interest policies.

2. Application Reviews
   
   In turn, the Director or a designee for the Division of Clinical Neuroscience and Behavioral Research, the Division of Epidemiology, Services and Prevention Research, the Division of Pharmacotherapies and Medical Consequences of Drug Abuse, and the Division of Basic Neuroscience and Behavioral Research presented their applications for consideration by the Council.  For each, Council provided concurrence with the initial scientific reviews en bloc.  Council also approved Method to Extend Research in Time (MERIT) Extension award and Administrative Supplements.   Relevant applications were presented to Council for Special Council Review, and Council agreed with program assessments. All Trans-NIH Initiatives, i.e., Common Fund applications and NIDA Secondary applications also received Council concurrence.
   
   Members must absent themselves from the Council meetings during discussion of, and voting on, individual applications from their own institutions or other applications in which there is a conflict of interest, real or apparent.  Conflicts of interest statements were signed by each member of the Council.  Members were not required to leave if an application in conflict with that member was acted upon en bloc.

Open Portion of the Meeting – September 3, 2014

1. Call to Order

   Dr. Nora Volkow, Director, NIDA, called the open portion of the meeting to order and welcomed all attendees.  She reminded the Council and audience that the meeting was open to the public in compliance with the Government in the Sunshine Act and indicated that time would be provided for public comment.  Dr. Volkow acknowledged the work of five retiring Council members, Drs. El-Bassel, Howell, Kirk, Mason and Picciotto, thanked them for their service to NIDA, and presented each with a certificate of appreciation.  She then called attention to future Council meetings: February 3-4, 2015, May 5-6, 2015, and September 1-2, 2015.  She reminded all attendees that the CRAN Council meeting will take place on February 4, 2015 and will be held at Fischer’s Lane.

2. Consideration of the Minutes of Council

   The Minutes of the NIDA May 2014 meeting were unanimously approved as written.

3. NIDA Director’s Report - Nora Volkow, M.D., Director, NIDA

   Dr. Volkow began her presentation with an update on the budget.  The projected budget for FY 2015 is $1,023,268, which is slightly higher than the FY 2014 budget of $1,014,591; however, the AIDS allocation will remain exactly the same at $300,714, approximately one third of the total budget.
   
   Turning to what is new at NIH; Dr. Volkow spoke about the new resubmission policy that was issued on April 17, 2014.   Ideas that were unsuccessfully submitted as a resubmission (A1) will now be allowed to be presented in a new grant application (A0) without having to substantially redesign the content and scope of the project.  There is a concern that this may result in more new A0 applications in FY 2015 and beyond, with potential to lower the success rates.
   
   Next, she spoke about the multi-prong approach NIH has taken to promote research reproducibility by developing online training modules for researchers in research design and methodology and by developing guidelines for researchers that are applying for grants.  These efforts are focused on preclinical studies, with priority given to those studies that have strong translational potential.  NIDA’s Dr. Elena Koustova is leading five activities on reproducibility: 1) Raising community awareness; 2) Enhancing formal training; 3) Piloting the reproducingtion of  selected NIDA-sponsored research projects; 4) Improving evaluation of applications; 5) Analyzing bias and irreproducibility risk reduction in animal studies.
   
   In addition, one of the major themes to be discussed at the upcoming Society for Neuroscience annual meeting on November 16, 2014 will be “Novel Methods and Technology Development: Enhancing Reproducibility of Neuroscience Studies.”  This session will be co-Chaired by Dr. Story Landis, Director of NINDS and Dr. Thomas Insel, Director of NIMH The panel, which will include NIDA’s Director, Dr. Nora Volkow, will be led by Dr. Francis Collins, Director NIH.  The goal is to summarize common causes of poor reproducibility; describe actions taken by the NIH and scientific publications to improve reliability; offer investigator perspectives; and address relevance for training.  Dr. Francis Collins will also lead a second presentation at the meeting to endorse the BRAIN initiative.
   
   Dr. Volkow then moved onto the NIH Blueprint Neurotherapeutics Network.  The purpose of this project is to generate and facilitate the identification of targets for use by pharmaceutical companies in areas that represent brain diseases.  Four grants will be funded, two of which relate to Alzheimer’s disease.   There is one study related to addiction diseases, specifically nicotine cessation led by Paul J. Kenney that is being considered for an additional 6 months of funding.  It hypothesizes that selective antagonists of orexin-1 receptor will reduce nicotine-seeking behavior without sleep effects associated with orexin-2 receptor.  Progress so far on this research has shown that a novel orexin-1 receptor antagonist decreases relapse-like behavior.  It attenuates cue-evoked nicotine seeking and decreases nicotine intake in rats at doses that do not affect response for food rewards.
   
   Dr. Volkow then spoke about the BRAIN initiative.  The top priority for this initiative is to develop tools and technologies that will allow scientists to understand how the brain works.  A BRAIN multi-council working group (MCWG) has been formed and set goals:  It has been tasked with providing scientific advice to the BRAIN Institutes and Centers staff and funding process to complement the expertise of the individual councils; members will ensure that each advisory council is informed about BRAIN initiatives, awards and progress; and a review of applications received for the BRAIN 2015 initiatives will be held on August 25^th.  As a result of this new development, NIDA is pleased to announce Mark Schnitzer from Stanford University as the new Council liaison to the working group.  Dr. Schitzer had been involved in the development of optical imaging tools and has been able to develop a little microscope that can be carried by rats.  These microscopes help to obtain simultaneous recordings of several hundred neurons based on calcium fluorescence imaging.
   
   Furthermore, six Funding Opportunity Announcements (FOAs) were published in 2014 to solicit applications for the BRAIN initiative:  1)  Cell-Type Classification (MH-14-215); 2)  Novel Tools- Cells and Circuits (MH-14-216); 3)  Next Generation Human Imaging (MH-14-217); 4)  Large Scale Recording & Modulation- New Technologies (NS-14-007); 5)  Large Scale Recording & Modulation- Optimization (NS-14-008); and 6)  Integrated Approaches to Understanding Circuit Function (NS-14-009).  All but number 5, listed above, will be re-issued in fiscal year 2015.  In addition, concepts for new initiatives include the following topics:  Micro-Scale Connectivity:  Benchmark data and transformative approaches; Human Brain Recording and Modulation: Multi-disciplinary teams to investigate human brain (dys)function and next generation human technologies; Multi-Scale Approaches:  Understand the biophysics and information content of macro-scale signals; Short Courses: Training in new technologies and data analysis and theory; and SBIR announcements:  BRAIN-affiliated SBIR, new technologies from small business.
   
   Another trans-NIH initiative that Dr. Volkow discussed is the Pain Consortium.  This initiative is managed by the NIH Office of Disease Prevention and it has been evaluating scientific literature to identify the role of opioids in the treatment of chronic pain.  Chronic pain is defined by the Pain Consortium as pain that lasts for more than three months or that persists after the insult has disappeared.  The goal is to answer the following inquiries:  1) Long-term effectiveness of opioids for treating chronic pain; 2) Potential risks of opioid treatment in various patient populations; 3) Effects of different opioid management strategies on outcomes related to addiction, abuse, misuse, pain and quality of life; 4) Effectiveness of risk mitigation strategies for opioid treatment; and 5) Future research needs and priorities to improve the treatment of pain with opioids.  The findings will be presented on September 29, 2014 at the Natcher Auditorium on the NIH Main Campus.  Dr. Volkow shared one study conducted by the Agency of Healthcare Research and Quality (AHRQ) through its Evidence-based Practice Centers (EPCs) on the Effectiveness and Risks of Long-term Opioid Treatment of Chronic Pain.  The report systematically reviewed current evidence on effectiveness and harms of opioid therapy for chronic pain, focusing on long term (>1 year) outcomes and was unable to identify any studies meeting the inclusion criteria.  In addition, where studies were available, the strength of evidence was rated no higher than low due to imprecision and methodological shortcomings.  She concluded this part of the presentation by stating that not only is there a need for research, but also a need to identify and select the questions with the greatest impact.
   
   Dr. Volkow moved onto current activities at NIDA.  She began by stating that the search for a Director for the soon to be created Division of Extramural Research (DER) and for the Director of the Division of Epidemiology Services and Prevention Research (DESPR) are both underway.
   
   Dr. Volkow then spoke about NIDA priority areas.  She began with the area of prevention by showing data from two main surveys on drug use in the United States.  The first one is the National Survey on Drug Use and Health, by SAMHSA and the second one is the Monitoring the Future (MTF) survey by University of Michigan.  There is a significant increase in the use of regular marijuana (defined as use of marijuana on 20 or more days per month) in persons aged 12 or older.   The MTF graph also showed that in recent years the perceived risk of regular marijuana use has been steadily trending down, and with it comes a sharp increase among 12 graders reporting regular use (up to 6.5% from the mid-1990s when it was around 2% regular use).  In addition, a more alarming trend is the increased regular use of marijuana among American Indians, with almost 15% of 12^th Graders.  And the initiation age of use is at 8 years of age, with 7% having tried it, and up to 60% by the age of 14 years.  There is a great need to better understand the consequences of these exposures in more vulnerable communities.
   
   Next, Dr. Volkow moved onto the ABCD, Adolescent Brain and Cognitive Development national longitudinal study that NIDA is leading along with NIAAA, NCI and NICHD.  A Request for Information was released in the summer and currently all recommendations for study design and measures are being summarized and will be presented at the Satellite Symposium at the Society of Neurosciences on November 17^th from 6:30 -8:30 p.m.  The Funding Opportunity Announcement is still expected to be published in early 2015.  She went on to state that this project has generated a great amount of interest, including among the international community.  Two main science journals, Nature and Science, had articles highlighting the importance of generating such a study.  Dr. Volkow reiterated the goals of the study are to understand the impact of various patterns and trajectories of substance exposure on brain structure and function; future Substance Use Disorders (SUD) or other psychopathology; and functional outcomes, including academic achievement, social development and other behaviors of public health importance.
   
   The second priority area was Treatment Interventions: New Targets and New Strategies.    Dr. Volkow highlighted two studies that evaluated the role of combination medications in the treatment of drug addiction.  In both studies, there was a significant and greater effect in abstinence rates from nicotine when Varenicline was given in combination vs. Varenicline alone.  The study by Jed Rose using Varenicline and bupropion combination therapy showed significant outcomes in men, and not necessarily in women.  Also, the outcomes are improved for those with a high cigarette consumption and nicotine dependence.  In addition, studies that looked at combination treatments suggest that the side effects are minimal, indicating that they are well tolerated.
   
   She added that the Division of Phamacotherapies and Medical Consequences of Drug Abuse (DPMCDA) led by Phil Skolnick has come up with a creative strategy to validate targets that are relevant in the treatment of drug addiction.  On September 8 and 9, 2014 a Targets Evaluation Meeting will be held where experts from the pharmaceutical industry will be evaluating 11 identified compounds/targets based on validation, feasibility and drug-ability.
   
   Dr. Volkow then presented Council members and the audience with a new NIDA FOA: The National Drug Abuse Treatment Clinical Trials Network (UG1), RFA-DA-15-008.  Through this FOA, NIDA intends to expand its research to develop and test interventions for the management of a wide spectrum of SUD with input from and collaboration with clinical investigators, healthcare providers, patients and relevant stakeholders.
   
   She then moved on to the HIV and Drugs priority area and began by presenting the 2014 Avant Garde Awardees.  Stephen Waggoner, Ph.D., Cincinnati Children’s Hospital Medical Center “A revolutionary vaccine approach to prevent HIV infection in substance abuse.”  He proposes preventing natural killer cells from destroying activated helper CD4 cells to strengthen vaccine effectiveness; Heinrich Gottlinger, M.D., University of Massachusetts Medical School “Mechanism of HIV cell-cell transmission of relevance to substance users.” He is studying the roles of two specific proteins involved in HIV’s movement from an infected to an uninfected cell; and Melanie Ott, M.D., Ph.D., Gladstone Institutes “A new model of accelerated immune aging in HIV-infected drug users.”  She is studying the role of an enzyme (SIRT-1) in slowing accelerated immune aging from either long-term HIV infection or drug use.
   
   She then added that HIV priorities across the NIH as a whole will be changing.  In November 2013, Francis Collins, Director of NIH, asked the Advisory Council for HIV to identify NIH top research priorities.  In June 2014, Dr. Jack Whitescarver, Director of Office of AIDS Research and NIH Associate Director for AIDS Research, presented 10 research priority areas:  Prevention, Treatment, STTR, Cure, Co-morbidities, Basic Science, Behavioral & Social Sciences, Implementation Science, Training, and Dissemination; with the greatest priority being towards the Cure initiative.  NIDA will emphasize two critical areas for a cure:  1) Towards a cure in brain (in vivo emphasis with in vitro components); 2) Towards a cure in substance using populations (in periphery).
   
   Dr. Volkow then spoke about and requested input from the Advisory Council members on the NIDA Strategic Plan that was initially developed in 2005 and last updated in 2010.  The substance abuse landscape has changed enormously since then and spans multiple topics from policy changes to legalization of marijuana, to health care reform that provides insurance to substance abusers, to the development of new administering technologies such as the electronic cigarette, and in the field of genetics such as epigenetic modification.  NIDA is requesting input from multiple sources:  NIDA program staff; NIDA Advisory Council members; Researchers; Constituent Organizations; Consumer Groups and other stakeholders.  It will use key mechanisms to gather input such as Bold Goals Challenge Prizes, Request for Information (RFI)/ Public Comments, and Priority Area/Cross-Cutting Work Groups.  The new Strategic Plan is expected to be published in the fall of 2015.
   
   Dr. Volkow finally shared the multiple Congressional Hearings that she, and/or NIDA Deputy Director, Dr. Wilson Compton have attended in the past three months.  She also presented the 2014 Intel International Science and Engineering Fair Addiction Science Awards winners, and a reminder of the upcoming November 14, 2014 Frontiers in Addiction Research Mini Convention that will be held at the Natcher Auditorium on the NIH Main Campus.
   
   Council thanked Dr. Volkow for her presentation.  One line of questions focused on the future of funding for behavioral scientists in the field of HIV/AIDS, especially as NIH shifts its priorities to more cure vs. prevention related studies.  A second question was posed related to the NIDA strategic plan and the use of metrics to measure success and reproducibility of the planned scientific portfolio, including the BRAIN Initiative and the ABCD Study.  Another Council member encouraged NIDA to pursue studies that combine diversity, social determinants of health, gender and specific effective interventions to help curb chronic relapsing addiction; also, for NIDA to continue to help inform healthcare policy  and clinical intervention studies in specific populations by funding drug tacking studies.  And lastly, comments to encourage funding of young emerging scientists and to provide strong mentorship in the field of addiction.

4. Federal Drug Control Policy and Priorities: How the Biomedical Research Community Can Help - Michael Botticelli, Acting Director of National Drug Control Policy, White House Office of National Drug Control Policy

   Mr. Botticelli began his presentation with an overview of the Office of National Drug Control Policy (ONDCP), its current activities and the importance of research for informing policy.  The ONDCP is a component of the Executive Office of the President, and was created by the Anti-Drug Abuse Act of 1988 to advise the President on drug-control issues.  By statute, ONDCP annually engages in three primary efforts to guide drug policy:  1) Develops the National Drug Control Strategy, which sets forth a comprehensive plan each year to reduce illicit drug use, the availability of drugs, and the consequences of drug use in the United States; 2) Develops a consolidated National Drug Control Program Budget to implement the Strategy; and 3) Coordinates and oversees the implementation by the Federal Drug Control Program Agencies of the policies, goals, objectives, and priorities established for the National Drug Control Program and the fulfillment of the responsibilities of such agencies under the Strategy.  These three activities guide the Administration’s efforts to reduce illicit drug use, manufacturing and trafficking, and drug-related crime and violence, and drug-related health consequences.  The Obama Administration is committed to restoring balance to U.S. drug-control efforts by coordinating an unprecedented government-wide public health and public safety approach to reduce drug use and its consequences.  Mr. Botticelli added that it is through this commitment that ONDCP is in the best position to advance a comprehensive public health approach for the delivery of substance use disorder intervention and treatment services, and works to ensure these services are not subsumed in a broader behavioral health care approach.  ONDCP’s goal is to make sure substance use disorder services remain a priority and is focusing on improving access to services and treating addiction across the continuum of care, from prevention and intervention to treatment and recovery.

   Mr. Botticelli provided a list of the office’s highest priorities for the remaining months of the Administration.  A large focus is on the devastating consequences of the opioid crisis, including prescription opioids, heroin and street fentanyl.  Furthermore, given the changes in the U.S. related to marijuana policy, including medical marijuana and decriminalization and regulation in certain States, it is imperative to learn more about marijuana’s effects on health and to support research on the potential therapeutic effects of cannabinoids.  Finally, improvements to treatment access are essential, and for opioids this means improvements in access to Medication-Assisted Treatment (MAT). 

   Mr. Botticelli noted that ONDCP creates targeted strategies for addressing major emerging issues.  He provided as an example that ONDCP and its Federal Partners, including NIDA, developed the Prescription Drug Abuse Prevention Plan to address the prescription drug abuse problem.  The plan, he added, focuses on addressing people who misuse prescription pharmaceuticals.  One of the questions they are trying to address is how to get the opioid prescriber community to engage in risk management and educational activities, and to better understand which tools would work for them.  Research is required to identify risks beyond bad patients and rogue prescribers; and trials are needed demonstrating the effectiveness of risk management tools like Prescription Drug Monitoring Program checks, urine testing, and adherence interventions; safe storage; pain management contracts; safe prescriber courses; naloxone prescription and overdose education.

   Mr. Botticelli then moved on to the subject of heroin use and showed a graph from the 2012 National Survey on Drug Use and Health conducted by SAMHSA.  The graph shows that despite efforts, there is still a large group of people who are opioid-misusing and dependent, as well as a trend in higher numbers of heroin use.  A second chart presented showed that based on the same study, approximately 8 million people in 2012 met criteria in the past year for substance use disorder, with 19% having sought treatment.  However, the majority, 74%, reported not entering or needing treatment.  A small percentage did not seek treatment because of motivational factors or because of barriers such as cost or lack of health insurance; but most did not go because of a perception that they did not require or need treatment.  There is a tremendous opportunity for ONDCP to help change this perceptual barrier, even without changing treatment effectiveness.

   Furthermore, as general practitioners start identifying more patients that require treatment, the patients need to have places that offer state of the art care.  ONDCPand its Federal partners are working to expand access to evidence-based treatment by: 1) Working with State Policy Teams to expand MAT for treatment of substance use disorders as standard of care; 2) Working with health plans and pharmacy organizations to offer adequate coverage for screening and treatment for substance use disorders, including MAT; 3) Working with Center for Medicare and Medicaid Services to inform states of substance use disorder health benefits that insurance policies should contain; and 4) Inventory treatment availability and work within Affordable Care Act (ACA) to ensure proper resourcing.  The ACA, he added, is the most significant piece of drug policy reform in generations.  By expanding insurance coverage, it extends coverage for addiction treatment to millions of Americans who need it.  Treatment, Mr. Botticelli emphasized, should be available to all who need it.

   He then moved on to the topic of marijuana and the need for research to provide credible factual information about it to parents, educators, and voters about the risks and associated costs.  Mr. Botticelli thanked NIDA for its efforts in studying both the good and ill effects of marijuana use and then provided a list of the questions ONDCP wants to answer:  What are the effects of marijuana and other cannabinoids on health and mental health?; How, why and to what extent do individuals differ in marijuana addiction susceptibility:  access vs. genes?; What are marijuana’s effects on society, including, educational attainment, employment and disability, work achievement, parenting, earnings, injury, and non-drug related crime?

   Finally, Mr. Botticelli concluded his presentation by stating that in his 2009 inauguration speech, President Obama pledged to “restore science to its rightful place and wield technology’s wonders to raise health care’s quality.”  ONDCP takes this promise seriously, and when available, uses science to inform its policies.  He then added that the research community can help by finding answers to priority research questions; disseminating policy-relevant findings; and informing development of the National Drug Control Strategy.

   Council members thanked Mr. Botticelli for his presentation and applauded ONDCP’s efforts at integrating and basing policy decisions on scientific and research-based evidence.

5. Women’s Health Research: Moving Forward - Janine Austin Clayton, M.D., NIH Associate Director for Research on Women’s Health, Director, NIH Office of Research on Women’s Health

   Dr. Clayton began her presentation by describing the mission of the Office of Research on Women’s Health (ORWH) and her approach in directing it.  The mission of the ORWH is to enhance, stimulate, and expand efforts to improve the health of women through biomedical and behavioral research, across the NIH; to examine the role of sex/gender in health and disease; and to promote recruitment, retention, reentry and advancement of women in biomedical careers. 

   She spoke about the history of ORWH and that it was formed in 1990 because of an advocacy movement; she spoke about some of the key women that have been involved since its inception at NIH; and how ORWH has evolved.  One of the key initiatives that the office is now implementing across NIH and its grantee community is the inclusion of women in research and studying the influences of sex/gender on health and disease from the preclinical (basic cell and animal) studies, to toxicology research, to the phase I, II and III clinical trials (sex-specific data analyses).

   Dr. Clayton proceeded by acknowledging NIDA’s work in leading the efforts of sex and gender in the continuum of research and how the former NIDA Director, Alan Leshner, had begun integrating this perspective throughout the institute’s entire research portfolio since 1998.  She then added that Dr. Nora Volkow, NIDA Director, is referred to as a science superstar by the staff at ORWH. She shared with the audience several of NIDA’s funding opportunity announcements and resulting publications that provide sex specific data.  In addition, ORWH and NIDA have been working collaboratively to fund administrative supplements, from which the “A to Z Guide: Sex and Gender Influences on Health” webpage uses NIDA supported research to inform and educate the community.

   She then shifted into the area of policy development as it relates to pre-clinical research and reproducibility.   NIH is committed to enhance reproducibility by setting policies to ensure that crucial experimental design elements such as blinding, randomization, replication, sample-size calculation and the effect of sex differences are well documented.  There has also been Congressional interest and inquiries related to males and females in preclinical research; for example, the Research for All bill that was recently introduced.  Dr. Clayton stated that this policy change is science driven and should be viewed as sex as a biological variable influencing science, influencing nature, influencing the understanding of a model, and influencing the understanding of a disease.  In addition, as a federal agency, NIH must be committed to understanding physiology and diseases in both sexes to maintain public trust and to enrich biological knowledge.

   Dr. Clayton then shared the conclusion of a study published in Neuroscience Biobehavioral Review 2014 March; 40:1-5.  It states that in a “meta-analysis of 293 articles, behavioral, morphological, physiological and molecular traits were monitored in male mice and females tested without regard to estrous cycle stage; variability was not significantly greater in females than males for any endpoint and was substantially greater in males for several traits.”  She then acknowledged that there are unique challenges to studying sex using cells, especially with authentication of cell lines; however, sex of origin knowable for cells derived from tissues and primary cells/cultures are easy to record and report.  Many journals are now requiring all manuscripts to indicate the sex of the animals used, or in the case of primary cells or culture, the sex of the animal from which they were derived.  These publications include, but are not limited to, Nature, The Lancet, Journal of the International AIDS Society, American Journal of Preventive Medicine, and Journal of Physiology.

   She then provided examples of current work that is being done around the NIH to support sex differences research, including the Specialized Centers of Research on Sex Differences that is supported by multiple institutes including NIDA, NICHD, NIAIMS, NIDDK, NIA, NIMH and the FDA.  Also, ORWH has an online sex and gender course that was developed in collaboration with the FDA; it contains three modules and provides continuing education credits.  One of the lessons available is on sex differences and substance abuse treatment.  Also, she presented the dates for the upcoming Advisory Committee on Research in Women’s Health, as well as other workshops and symposia. 

   Dr. Clayton concluded her presentation by discussing one of NIH’s mission areas of promoting women in biomedical careers.  Funding was provided to several grantees to examine the causal factors and interventions affecting women in biomedical careers.  The results show that senior leadership support for women’s career advancement is essential; unconscious bias is real, but it can be measured and changed; culture affects career satisfaction and performance, and it too can be measured and changed; mentor networks are more effective than mentor dyads; and institutional flexibility policies are under-recognized and under-used, in part due to ingrained academic culture and lack of leadership buy-in.  

   Dr. Volkow and Council members thanked Dr. Clayton for her presentation and applauded ORWH’s efforts on working on a comprehensive policy that will improve sex difference research and reproducibility.

6. Epigenomics Program Update - John Satterlee, Ph.D., Roadmap Epigenomics Program, Co-coordinator Program Director: Epigenetics, Model Organism Genetics and Functional Genomics
   DBNBR, NIDA

   Dr. Satterlee began his presentation with an objective to provide Council members with an update on the epigenomics program at NIDA, at NIH, and beyond.   He began by stating that all the cells in our bodies have more or less the same genome; and yet, transcriptional factors and epigenomic regulation are what lead to the many different cell types.  Epigenomic changes have been implicated in a wide variety of diseases.  Development and cellular differentiation can impact the epigenome, but also external influences including diet and drugs of abuse.  There is increased interest among the scientific community in the area of neuroepigenetics and Dr. Statterlee shared a graphic that demonstrated a sharp increase in the number of publications in this area from 2005 with close to 50 publications, to over 500 publications in year 2013.

   He then provided the definitions for both epigenetics, which is the study of heritable or long lasting changes that are not caused by changes in the DNA sequence; and epigenome, which are all of the epigenetic marks for a cell type.  There are at least three major ways that epigenetic regulation occurs: 1) through direct modification of the DNA, 2) through modifications of the histone proteins, and 3) through non-coding RNAs that can also regulate the chromatin.

   Dr. Satterlee then presented epigenetics at NIDA and showed how many grants both NIDA and the OD Common Fund have been funding from 2005 through 2014.  Research is being conducted on epigenetic changes in the brain resulting from the use of cocaine, nicotine, methamphetamine, cannabinoids, opioids, and alcohol in order to study the molecular mechanisms of substance use disorders, biomarkers, intergenerational effects, new targets for therapeutics, and epigenetic therapeutics.  He then provided examples of current NIDA funded research that is looking at epigenetic therapeutics in the use of histone deacetylase-3 inhibitors and cocaine seeking behavior; morphine exposure and its associated intergenerational effects; and the effects of cocaine exposure on reprogramming the sperm epigenome.

   Following that, he described the epigenomics project via the Common Fund, which is co-chaired by Dr. Nora Volkow, and consists of other NIDA staff including Ms. Dena Procaccini and Dr. Joni Rutter.   There are multiple components to the project.  Mapping centers will generate comprehensive epigenomic maps for normal human cells and tissues.  The lead for the analysis of this component of the program is Dr. Manolis Kellis, who has written an integrative paper analyzing 92 epigenomes.  The data can be used for multiple purposes and he provided examples, such as predicting what cell types might be involved in a disease, even before fully understanding the disease.  Another component of the project is revolutionary technology development to significantly change epigenetics research.  The success of the program has been measured, so far, by the number of publications, and also by the number of citations of the data and papers to conduct further research. 

   He then transitioned into the goal of the International Human Epigenome Consortium (IHEC), which is to generate 1,000 reference epigenomes and to understand the epigenomic basis of disease.  Member countries, which are the EU, Canada, Germany, Japan, South Korea and Singapore, have invested a total of $125 million in non-US effort to generate comprehensive reference epigenomes, common data standards, rapid data sharing, training and related technologies.  Dr. Statterlee thanked his colleague, Ms. Dena Procaccini of NIDA for her work and efforts in overseeing the continuation of the projects supported by the IHEC.

   Last, Dr. Satterlee discussed future research plans and ambitions for the field of epigenomics.  In particular, he supports interpretation of genome-wide association studies, especially for brain disorders to better understand the cell types that are involved.  Another area of research is validation of animal epigenetic studies in human post-mortem.   He also suggested the area of in- vivo epigenetic imaging and biomarkers for chronic drug exposure or other phenotypes.  And finally, he spoke about perdurance and prevention in terms of answering how long do the epigenetic changes due to environmental exposures last and are they reversible; as well as intergenerational inheritance and the importance of validating study results to determine whether or not the transmission is epigenetic, and if so, what are ways to protect epigenomes for future generations.

   NIDA Council members thanked Dr. Satterlee for his dedication to this issue and for implementing so many profound programs.  Council members encouraged, as applicable by the research, efforts to study samples from diverse populations, as well as both genders.
    

7. There were no Public Comments

8. Adjourn

   The 118^th meeting of the National Advisory Council on Drug Abuse was adjourned at 12:00 p.m.

Certification

I hereby certify that the foregoing minutes are accurate and complete.

Note: Informational materials provided to the public at the open session of the meeting may be obtained from the Executive Secretary.